Focus
Authors: Daniel Shouval
Journal: Journal of Hepatology (2012)

Liver transplantation for acute liver failure in Europe: Outcomes over 20 years from the ELTR databaseJournal of HepatologyVol. 57Issue 2PreviewLiver transplantation for acute liver failure (ALF) still has a high early mortality. We evaluated changes during 20 years, and identified risk factors for poor outcome. Full-Text PDF Conservative as well as surgical management through liver transplantation (LT) for patients with acute liver failure (ALF) has been constantly improving for the past three decades. Data on the long-term prognosis of patients with ALF who underwent LT are scarce. Consequently, the two large data bases, namely the US UNOS [[1]2009 Annual Report of the US Organ Procurement Transplant Network and Scientific Registry of Transplant Recipients: Transplant data 1999–2008. Available from <http://optn.transplant.hrsa.gov/ar2009>.Google Scholar] and the European Liver Transplant Registry (ELTR) [[2]<http://www.eltr.org>.Google Scholar], have been invaluable resources which had a major impact on a remarkable progress in the management of such patients. The ELTR data base contains selective information collected since 1968 and from 1985 prospectively, on LT performed in over 87,000 patients in 143 centers and 25 European countries [2<http://www.eltr.org>.Google Scholar, 3Adam R. McMaster P. O’Grady J.G. Castaing D. Klempnauer J.L. Jamieson N. et al.Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry.Liver Transpl. 2003; 9: 1231-1243Crossref PubMed Scopus (495) Google Scholar]. The registry contains a wealth of information on a wide range of parameters including epidemiological and demographic characteristics of liver donors and recipients, quality and size of the grafts, complications of surgery, survival and more. In the present issue of the Journal, Germani and co-workers have used the ELTR data base to analyze the risk factors which govern the up to 10 year survival rates of patients and grafts in ALF patients who underwent LT [[4]Germani G. Theocharidou E. Adam R. et al.Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database.J Hepatol. 2012; 57: 288-296Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar]. The studied associated risk factors include among others, the etiology of ALF, donor and recipient age, gender, blood group matching, total ischemic time of the graft, graft type, surgical technique, and causes of graft failure or death. These were evaluated in a cohort of 4903 adults who underwent LT between 1988 and 2009 [[4]Germani G. Theocharidou E. Adam R. et al.Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database.J Hepatol. 2012; 57: 288-296Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar]. Space limitations for comments do not enable a detailed discussion of data. However, several conclusions can be drawn from the major findings of this important study: Survival of grafts and patients in Europe has improved significantly for the years 2004–2009 as compared to three previous 4–5 year periods between 1988 and 2003. Although mortality during the first year after LT for ALF still remains relatively high, the recent 1, 5, and 10 years patients/graft survival rates were 74/63%, 68/57%, and 63/50%, respectively. The increased survival rates of European ALF patients are especially evident in the cohort of 2004–2009 LT patients. Data presented in Figs. 2A and B, suggest indeed a progressive improvement in survival, especially in the first year post LT. This is most likely the consequence of improvement in a number of factors including intensive and medical care, in surgical techniques and experience as well as in efficacy of anti-rejection agents. As also shown in the US, long-term survival of ALF patients after LT is lower as compared to results in patients with chronic liver disease (CLD). There are some minor differences in reports on survival rates of ALF patients one year after LT between patients in the US and Europe at 82% and 74%, respectively. However, such a comparison is inaccurate and does not diminish the importance of the continuous advance in the management of patients which has occurred despite a 10-fold rise in the rates of organ donors above the age of 60 years. In this study, the investigators employed 3- and 12-month prognostic models to identify potential risk factors associated with the relatively high mortality of ALF patients in the first year post ALT. Despite some limitations, mainly regarding the 12-month model, the results obtained through these tools suggest that the major risk factors with a detrimental impact on mortality post LT include, donor age >60 years, recipient age >50 years, the use of reduced size grafts and incompatible ABO blood group matching. Although known for several years, one finding of the present analysis is of particular concern, namely the 7-fold rise from 2.0% to 14.1% in the number of patients undergoing LT for paracetamol-induced ALF. Not less disturbing is the 8% loss of graft or life due to repeated suicide or lack of compliance. These data suggest that such patients need a very close post transplant support including better social and psychologic care. Ideally, such high risk patients should be identified prior to referral for LT. However, the urgency in performing LT usually prevents an in depth psychiatric analysis pre-transplant. As also acknowledged by the investigators, there are some limitations in the use of the ELTR data base in the models for the assessment of prognosis of LT patients in this study. These include the lack of information regarding pre-transplant renal function, ventilation status, as well as degree of hepatic encephalopathy and brain edema. Furthermore, the etiology of fulminant hepatitis is highly variable in different geographic regions within Europe which has an impact on pre and post transplant prognosis. For example, paracetamol intoxication is more prevalent in the UK and Northern Europe. In contrast, viral hepatitis B and A, although in decline following introduction of vaccination and anti-viral therapy, are more prevalent in Southern European countries. In summary, taking into account some limitations of the structure of ELTR data base and analysis of the large set of data, this extensive report provides a wealth of information which is of great value to hepatologist, intensive care experts, and surgeons taking care of these sick ALF patients. Despite the major progress made in our ability to predict the probability of spontaneous recovery of patients with ALF, this remains an ongoing and difficult challenge. Following the analysis in the discussed report, the task becomes even more difficult. When bad prognostic factors such as older age of donor and recipient as well as ABO mismatch and/or use of reduced graft size cluster together, such circumstances suggest that survival after LT will be significantly impaired and mortality may reach >50%, a figure which appears unacceptable. The author declared that he does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.